About

Michele P Lambert, MD, MTR, is an Associate Professor of Pediatrics (Hematology) at the Children's Hospital of Philadelphia. She holds roles as an Attending Physician in the Division of Hematology at the Children's Hospital of Philadelphia, a Consulting Attending Physician in the Section of Hematology/Oncology at Pennsylvania Hospital, and a Consulting Physician in the Section of Newborn Pediatrics at the Hospital of the University of Pennsylvania. Dr. Lambert is also the Medical Director of the Special Coagulation Laboratory in the Department of Pathology and Laboratory Medicine at Children's Hospital of Philadelphia, and co-directs the Frontier Program in Immune Dysregulation there. Additionally, she serves as the Director of the Pediatric Platelet Disorder Program in the Division of Hematology at the same institution.

Research topics

• Medicine
• Internal medicine
• Immunology
• Biology
• Genetics
• Virology
• Bioinformatics
• Computational biology
• Pathology
• Gastroenterology

Selected publications

• Comprehensive Serum Proteome Profiling of Cytokine Release Syndrome and Immune Effector Cell–Associated Neurotoxicity Syndrome Patients with B-Cell ALL Receiving CAR T19

  Clinical Cancer Research · 2022 · 61 citations

  • Medicine
  • Immunology
  • Biology

  PURPOSE: To study the biology and identify markers of severe cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in children after chimeric antigen receptor T-cell (CAR T) treatment. EXPERIMENTAL DESIGN: We used comprehensive proteomic profiling to measure over 1,400 serum proteins at multiple serial timepoints in a cohort of patients with B-cell acute lymphoblastic leukemia treated with the CD19-targeted CAR T CTL019 on two clinical trials. RESULTS: We identified fms-like tyrosine kinase 3 (FLT3) and mast cell immunoglobulin-like receptor 1 (MILR1) as preinfusion predictive biomarkers of severe CRS. We demonstrated that CRS is an IFNγ-driven process with a protein signature overlapping with hemophagocytic lymphohistiocytosis (HLH). We identified IL18 as a potentially targetable cytokine associated with the development of ICANS. CONCLUSIONS: We identified preinfusion biomarkers that can be used to predict severe CRS with a sensitivity, specificity, and accuracy superior to the current gold standard of disease burden. We demonstrated the fundamental role of the IFNγ pathway in driving CRS, suggesting CRS and carHLH are overlapping rather than distinct phenomena, an observation with important treatment implications. We identified IL18 as a possible targetable cytokine in ICANS, providing rationale for IL18 blocking therapies to be translated into clinical trials in ICANS.

  DOI

• Glanzmann thrombasthenia: genetic basis and clinical correlates

  Haematologica · 2020 · 144 citations

  • Medicine
  • Internal medicine
  • Immunology

  genes and form platelet glycoprotein (GP)IIb/IIIa, which acts as the principal platelet receptor for fibrinogen. Although there is variability in the clinical phenotype, most patients present with severe mucocutaneous bleeding at an early age. A classic pattern of abnormal platelet aggregation, platelet glycoprotein expression and molecular studies confirm the diagnosis. Management of bleeding is based on a combination of hemostatic agents including recombinant activated factor VII with or without platelet transfusions and antifibrinolytic agents. Refractory bleeding and platelet alloimmunization are common complications. In addition, pregnant patients pose unique management challenges. This review highlights clinical and molecular aspects in the approach to patients with GT, with particular emphasis on the significance of multidisciplinary care.

  DOI

• Whole-genome sequencing of a sporadic primary immunodeficiency cohort

  Nature · 2020 · 238 citations

  • Biology
  • Genetics
  • Medicine
  DOI

• Whole-genome sequencing of patients with rare diseases in a national health system

  Nature · 2020 · 575 citations

  • Computational biology
  • Biology
  • Genetics
  DOI

• Multisystem inflammatory syndrome in children and COVID-19 are distinct presentations of SARS–CoV-2

  Journal of Clinical Investigation · 2020 · 414 citations

  • Medicine
  • Immunology
  • Virology

  BACKGROUNDInitial reports from the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic described children as being less susceptible to coronavirus disease 2019 (COVID-19) than adults. Subsequently, a severe and novel pediatric disorder termed multisystem inflammatory syndrome in children (MIS-C) emerged. We report on unique hematologic and immunologic parameters that distinguish between COVID-19 and MIS-C and provide insight into pathophysiology.METHODSWe prospectively enrolled hospitalized patients with evidence of SARS-CoV-2 infection and classified them as having MIS-C or COVID-19. Patients with COVID-19 were classified as having either minimal or severe disease. Cytokine profiles, viral cycle thresholds (Cts), blood smears, and soluble C5b-9 values were analyzed with clinical data.RESULTSTwenty patients were enrolled (9 severe COVID-19, 5 minimal COVID-19, and 6 MIS-C). Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C.CONCLUSIONPediatric patients with SARS-CoV-2 are at risk for critical illness with severe COVID-19 and MIS-C. Cytokine profiling and examination of peripheral blood smears may distinguish between patients with MIS-C and those with severe COVID-19.FUNDINGFinancial support for this project was provided by CHOP Frontiers Program Immune Dysregulation Team; National Institute of Allergy and Infectious Diseases; National Cancer Institute; the Leukemia and Lymphoma Society; Cookies for Kids Cancer; Alex's Lemonade Stand Foundation for Childhood Cancer; Children's Oncology Group; Stand UP 2 Cancer; Team Connor; the Kate Amato Foundations; Burroughs Wellcome Fund CAMS; the Clinical Immunology Society; the American Academy of Allergy, Asthma, and Immunology; and the Institute for Translational Medicine and Therapeutics.

  DOI

Recent grants

• NIH Grant K23HL092164

  NIH · $781k · 2013

Frequent coauthors

• Jenny M. Despotovic

  Agios Pharmaceuticals (United States)

  174 shared

• James B. Bussel

  Cornell University

  151 shared

• Rachael F. Grace

  Harvard University

  122 shared

• Michael D. Tarantino

  Bleeding & Clotting Disorders Institute

  111 shared

• Keith R. McCrae

  109 shared

• Terry Gernsheimer

  University of Washington

  108 shared

• Jay H. Herman

  Thomas Jefferson University

  100 shared

• David T. Teachey

  Children's Hospital of Philadelphia

  92 shared

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